The goal of this project is to develop chip-based DNA sensor arrays and instruments for mutation detection based on a decade of research on DNA-mediated electron transfer chemistry. Electron transfer through a DNA helix can be interrupted by a single-based mismatch irrespective of the DNA sequence composition, mismatch position and identity. This unique property offers significant advantages when it is applied to mutation detection for cancer predisposition and diagnostic. To distinguish a very small difference in hybridization energy between fully matched and single-based mismatched DNA helixes, the popular hybridization based methodology requires extensive manipulation of hybridization conditions as well as sophisticated deconvolution algorithms. This proposal aims to take advantages of the high sensitivity of the DNA-mediated electrochemistry to the stacking in DNA helixes and develop miniaturized , integrated, portable DNA sensors on a chip platform to detect mutations in multiple genes in a parallel fashion. In Phase I, feasibility of implementing the DNA-mediated electrochemistry on chip platform will be established. Mutational analysis of hotspots in p53 tumor suppressor gene will be demonstrated. PROPOSED COMMERCIAL APPLICATIONS= Not Available